Since it has been formulated, considerable progress have been made on this question [1]}, [2]}, [3]}, [4]}, [5]}, [6]}, [7]}, [8]}, [9]}, [10]}, [11]}, [12]}, [13]}, [14]}, [15]}. However, conventional theoretical approaches still state that a genotype mutates into another through point mutations (e.g. single-nucleotide variations). If one takes a look at the molecular scale of DNA and the different mutation types, this may seem contradictory as it is well known that many other kinds of variation operators (including insertions, deletions, duplications, translocations and inversions) act on the genome. Hence, a fundamental aspect of this challenge is to understand—at the scale of molecular evolution—the roles played by these different mutation types. Indeed, there is a gap between the theoretical models, that account for a very limited set of mutations types—typically only point mutations—and the reality of molecular evolution, where multiple variation operators act on the sequence.
